Organotherapy Articles 9

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Organotherapy
            (Bernhardt, 2013) Download
In the Muenchener Medizinische Wochenschrift, No. 16, 1912, the author described a severe case of diffuse sclerodermia treated with cœliacin, which is an extract of the mesenteric glands. The case as previously described, had improved greatly under the treatment, which consisted of one tablet three times a day, each tablet corresponding to 0.3 g. of the dried gland substance. The patient was under observation 11⁄2 years, at the end of which time she had gained 24 pounds in weight and the skin was practically normal, except the hands and feet, these, however, having greatly improved.

Organotherapy, British physiology, and discovery of the internal secretions.
            (Borell, 1976) Download
In April 1891, the French physiologist and neurologist C.E.Brown- Sequard (1817-1894) and his assistant Arsene d'Arsonval (1851-1940) suggested to the Society of Biology at Paris that potent substances, which they called "internal secretions," ought to exist in animal tissues, and that disease probably resulted from their lack. Organotherapy as this form of therapy came to be called, had originated two years earlier in Brown-Sequard's rejuvenation studies.

Gross thymic extract, Thymax, induces apoptosis in human breast cancer cells in vitro through the mitochondrial pathway.
            (Ghoneum et al., 2008) Download
Previous studies have shown that thymic extracts possess antitumor and antimetastatic properties, but the mechanisms are not completely understood. Therefore, in this study the ability of the gross thymic extract Thymax to induce apoptosis in human breast cancer cell line (MCF-7) cells in vitro was evaluated. Tumor cells were cultured with different concentrations of Thymax for 24 h and the apoptotic response was assessed by propidium iodide and TUNEL assays. Activation of caspases and changes in mitochondrial membrane potential (MMP) were monitored by flow cytometry and the expression of Bcl-2 and Bax was determined by Western blot analysis. Thymax induced apoptosis in monolayer MCF-7 cells in a dose-dependent manner; at concentrations of 2.5, 5 and 10% (v/v) it caused 9%, 10% and 25% apoptosis, respectively, as compared to 6% for control cancer cells without treatment. The induction of apoptosis by Thymax was associated with activation of caspases 8 and 9, and the addition of a pan caspase inhibitor partially inhibited Thymax-induced apoptosis by 20%. In addition, the MMP was decreased significantly at Thymax concentrations of 5%-20%, which was associated with a decrease in the protein expression of Bcl-2 and an increase in Bax. These results suggest that Thymax exerts its effects via the mitochondrial pathway of apoptosis and may represent a new class of adjuvants for the treatment of breast cancer.

Activation of human monocyte-derived dendritic cells in vitro by Thymax, a gross thymic extract.
            (Ghoneum et al., 2009a) Download
BACKGROUND:  We have recently demonstrated that Thymax, a gross thymic extract, induces an apoptotic effect against human breast cancer cells. In this study, the ability of Thymax to activate human dendritic cells (DCs) and the DC-directed T-cell response was examined in an in vitro culture model of peripheral blood mononuclear cells. MATERIALS AND METHODS:  The level of costimulatory molecules (CD40, CD80, CD83, CD86) and T-cell proliferation were analyzed by flow cytometry. Cytokine secretion was measured by ELISA. RESULTS:  Thymax activated DCs to secrete interleukin (IL)-12p40 and IL-6 cytokines and inhibited IL-10 production. Additionally, Thymax caused the up-regulation of CD80 and CD86 in DCs, leading to an increase in CD4(+) T-cells, which subsequently induced secretion of interferon-gamma (IFN-gamma). CONCLUSION:  Taken together, the data showed that Thymax activated DCs and, consequently, Th1 cells. Thus, Thymax is an immune-activating compound that needs to be evaluated extensively for its possible therapeutic properties.

Phenotypic correction of Age-associated functional decline in murine immune cells by Thymax, a thymic extract.
            (Ghoneum et al., 2009b) Download
BACKGROUND:  We have recently demonstrated that Thymax, a gross thymic extract, induces the functional activity of human dendritic cells (DCs) in vitro. In this study, the role of Thymax in phenotypic correction of age-associated functional decline in immune cells in mice was evaluated. MATERIALS AND METHODS:  C57BL/6 mice (13 months old) were treated with Thymax orally (20% v/v) for 4 weeks. Different splenic cell types, dendritic cells (DCs), B-cells, T-cells and natural killer (NK) cells, were analyzed using flow cytometry. RESULTS:  Treatment with Thymax resulted in: i) a significant increase in the percentages of DCs (1.6-fold), B-cells (7-fold) and T-cells (5-fold) over the control (p<0.05); ii) an increase in the percentages of activation markers (CD25 and CD69) of CD4(+) and CD8(+) T-cells; and iii) an enhancement in NK activity. Thymax showed no adverse side-effects. CONCLUSION:  Thymax might have a role in reversing immune dysfunction in the elderly.

Hormones and the Bolsheviks: from organotherapy to experimental endocrinology, 1918-1929.
            (Krementsov, 2008) Download
The discipline of endocrinology emerged over roughly the same period in Britain, France, Germany, Russia, the United States, and elsewhere, and its practitioners across the world shared research practices and agendas to a considerable degree. Yet the discipline's institutions, networks, and social practices were firmly embedded in the particular social fabric of concrete locales, and they were built on specific local traditions, resources, and patronage. Through analysis of the origins and early progress of Soviet endocrinology, this essay uncovers numerous factors and multiple actors involved with the institutional development of the discipline in the first decade of Bolshevik rule. As elsewhere in the world, the medicinal use of animal tissue extracts--organotherapy--paved the way for wide acceptance of the ideas of the nascent science of endocrinology by both the Soviet medical community and the general public. Organotherapy also supplied the new discipline with "seed" institutions, technologies, and personnel--the veterinarian Iakov Tobolkin and the therapist Vasilii Shervinskii. But the specific institutional, political, economic, and ideological landscape of Soviet Russia shaped the discipline in a particular way.

Steroids in arms: science, government, industry, and the hormones of the adrenal cortex in the United States, 1930-1950.
            (Rasmussen, 2002) Download
From the late nineteenth century to the 1940s, endocrinology was one of the most dynamic areas of biomedical research, despite a certain aura of quackery that gathered around the field in its earliest years, generated precisely by its perceived promise (which provoked a proliferation of unrefined organ extract treatments for popular ailments such as impotence and hysteria). Together with bacteriology, endocrinology was one of the first areas in which the life sciences established their direct utility in clinical medicine, with the milestone 1891 demonstration that extract of thyroid glands was efective in treating the well-defined clinical deficiency condition myxoedema.

'Shotgun therapy': the understanding and use of thyroid organotherapy in Britain, 1890-1925.
            (Tam, 2007) Download
The hormone concept s a relatively new facet of medicine, arguably first proposed by the French physiologist Claude Bernard in 1885.

 


References

Bernhardt, MS (2013), ‘Organotherapy.’, JAMA Dermatol, 149 (12), 1366. PubMed: 24352719
Borell, M (1976), ‘Organotherapy, British physiology, and discovery of the internal secretions.’, J Hist Biol, 9 (2), 235-68. PubMed: 11610067
Ghoneum, M, et al. (2008), ‘Gross thymic extract, Thymax, induces apoptosis in human breast cancer cells in vitro through the mitochondrial pathway.’, Anticancer Res, 28 (3A), 1603-9. PubMed: 18630518
Ghoneum, M, Y Seto, and S Agrawal (2009a), ‘Activation of human monocyte-derived dendritic cells in vitro by Thymax, a gross thymic extract.’, Anticancer Res, 29 (11), 4367-71. PubMed: 20032380
Ghoneum, M, L Tolentino, and Y Seto (2009b), ‘Phenotypic correction of Age-associated functional decline in murine immune cells by Thymax, a thymic extract.’, In Vivo, 23 (6), 895-902. PubMed: 20023230
Krementsov, N (2008), ‘Hormones and the Bolsheviks: from organotherapy to experimental endocrinology, 1918-1929.’, Isis, 99 (3), 486-518. PubMed: 18959193
Rasmussen, N (2002), ‘Steroids in arms: science, government, industry, and the hormones of the adrenal cortex in the United States, 1930-1950.’, Med Hist, 46 (3), 299-324. PubMed: 12194423
Tam, CK (2007), ‘Shotgun therapy: the understanding and use of thyroid organotherapy in Britain, 1890-1925.’, Pharm Hist (Lond), 37 (4), 50-56. PubMed: 18447305